Cognition, Behavior, and Memory
Author: Jesus Villalobos Vasquez | Email: jvillalobosvasquez1984@gmail.com
Jesus Villalobos Vasquez1°, Virginia Silvana Pérez1°,Graciela Noemí Balerio1°2°
1° Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Investigaciones Farmacológicas (ININFA-CONINCET))
2° 2Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Farmacología
Previous studies revealed sex differences in behavioural, molecular and biochemical responses to morphine (MOR) withdrawal. On the other hand, the stress is one of the factors that induces relapse to drug abuse. This study explored the role of the cannabinoid system in MOR reinforcing effects, extinction, and relapse of these effects in wild-type (WT) and CB1 receptor knockout (KO CB1) of CD1 mice of both sexes. The reinforcing effects of MOR (10 mg/kg, sc) was confirmed by using the conditioned place preference paradigm, followed by an extinction phase with 10 saline sessions (0.10 ml/g, sc) and a stress-tested relapse due to immobilization. Results showed a reinforcing effect of MOR in both sexes of WT and KO CB1 mice (p<0.05), being more intense in KO CB1 mice (p<0.05). The extinction of reinforcing effects was also observed in both sexes and genotypes, but WT females showed a higher extinction (p<0.05) than males, while relapse was only observed in WT females which had extinguished the reinforcing effects (p<0.05). Although the reinforcing effects of MOR showed no significant sex differences, it was more intense in KO CB1 mice compared to WT mice. In addition, stress-induced relapse occurred only in WT females, but not in KO CB1 mice. In conclusion, these findings suggest the involvement of the cannabinoid system in the rewarding effects of MOR and its stress-induced relapse, highlighting the CB1 receptor as a potential target for sex-specific opioid addiction therapies.